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Daniel G Oliveira,1 Raquel Faria,2,3 Tiago Torres3,4 1Department of Internal Medicine, Centro Hospitalar e Universitário do Porto, Porto, Portugal; 2Clinical Immunology Unit (UIC), Centro Hospitalar e Universitário do Porto, Porto, Portugal; 3Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar – University of Porto, Porto, Portugal; 4Department of Dermatology, Centro Hospitalar e Universitário do Porto, Porto, PortugalCorrespondence: Tiago TorresDepartment of Dermatology, Centro Hospitalar Universitário do Porto, Rua D. Manuel II, s/n, ex-CICAP, Porto, 4099-001, PortugalEmail torres.tiago@outlook.comAbstract: Psoriatic arthritis is a complex and heterogeneous disease with potential significant disability and impaired quality of life. Although in the last decades new treatment options have led to a better management of this disease, there are still significant unmet therapeutic needs. Dual inhibitor antibodies target two different cytokines simultaneously, potentially offering a better disease control. In psoriatic arthritis, there is evidence for a pathogenic role not only of IL-17A but also the structurally homologous IL-17F. It is postulated that differential expression of both in several targets of PsA could account for disparities in clinical response to IL-17A inhibition alone (such as with secukinumab or ixekizumab). Here we review the evidence so far for the use in psoriatic arthritis of bimekizumab, the first humanized monoclonal IgG1 antibody that selectively neutralizes both IL-17A and IL-17F. A Phase 2b trial reports better outcomes over both placebo and IL-17A inhibition alone. Very recently encouraging results from open-label extensions with regards to both safety and maintenance of response were presented. Phase III trials are ongoing with the first results awaited in 2021.Keywords: psoriatic arthritis, psoriasis, bimekizumab, interleukin-17A, interleukin-17F, biologic therapy

Egídio Freitas,1 Maria Alexandra Rodrigues,1 Tiago Torres1,2 1Department of Dermatology, Centro Hospitalar e Universitário do Porto, Porto, Portugal; 2Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, PortugalCorrespondence: Tiago TorresServiço de Dermatologia Centro Hospitalar do Porto, Rua D. Manuel II, s/n Piso 1, Porto 4050-344, PortugalTel/ Fax +351 226097429Email torres.tiago@outlook.comAbstract: Palmoplantar pustulosis (PPP) is a rare, chronic, recurrent inflammatory disease that affects the palms and/or the soles with sterile, erupting pustules, which are debilitating and usually resistant to treatment. It has genetic, histopathologic and clinical features that are not present in psoriasis; thus, it can be classified as a variant of psoriasis or as a separate entity. Smoking and upper respiratory infections have been suggested as main triggers of PPP. PPP is a challenging disease to manage, and the treatment approach involves both topical and systemic therapies, as well as phototherapy and targeted molecules. No gold standard therapy has yet been identified, and none of the treatments are curative. In patients with mild disease, control may be achieved with on-demand occlusion of topical agents. In patients with moderate-to-severe PPP, phototherapy or a classical systemic agent (acitretin being the best treatment option, especially in combination with PUVA) may be effective. Refractory patients or those with contraindications to use these therapies may be good candidates for apremilast or biologic therapy, particularly anti-IL-17A and anti-IL-23 agents. Recent PPP trials are focusing on blockage of IL-36 or IL-1 pathways, which play an important role in innate immunity. Indeed, IL-36 isoforms have been strongly implicated in the pathogenesis of psoriasis. Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore the diagnosis, screening and treatment of patients with PPP.Keywords: palmoplantar pustulosis, palmoplantar pustulosis psoriasis, IL36, ANB019, spesolimab

Álvaro Machado,1 Tiago Torres1,2 1Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal; 2Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal Abstract: Psoriasis is a common chronic immune-mediated skin disease, with systemic involvement and significant impact in patients’ quality of life. Several highly specific treatments have been developed over the years, such as tumor necrosis factor-α inhibitors, a nonselective IL-23 inhibitor (ustekinumab), and most recently IL-17 inhibitors. Risankizumab is a monoclonal antibody which targets IL-23p19 without binding IL-12. This novel therapeutic approach is expected to have advantages over the recently approved anti-IL-17 agents, such as the avoidance of Candida infections and neutropenia. In addition, unlike ustekinumab, the selective inhibition of IL-23 may preserve IL-12-dependent functions such as protection against infections and tumor immune surveillance. Risankizumab showed an excellent efficacy when compared to placebo and ustekinumab, with higher Psoriasis Area Severity Index (PASI) 75, PASI 90, and PASI 100 rates, along with a convenient every 12-week maintenance dosing regimen. Overall, risankizumab was well tolerated and the most common adverse event was upper respiratory tract infection. In the near future, further data will be available not only in psoriasis but also in Crohn’s disease and psoriatic arthritis fields. Head-to-head trials comparing risankizumab with other IL-23 inhibitors and with IL-17 inhibitors will be crucial to reveal the role of risankizumab in the treatment of psoriasis. Keywords: psoriasis, IL-23, risankizumab

The thermal decomposition of strontium carbonate in the SrCO3-Al2O3-SrSO4 system was studied by thermal analysis under isothermal experiments. Powder of reactive grade of SrCO3, Al2O3 y SrSO4 in molar ratio 3:3:1 were prepared. The powders were heat treated from 750 to 1000 °C for 4 h. Loss weight for each temperature was registered and the kinetics parameter were determine using the classical fit method. The effect of mechanical activation of SrCO3 was studied as well. The reaction mechanism for 750 to 900 °C temperature range corresponded to a geometric shrinkage in the grain boundary (R1.1) with an activation energy of 106. 21 Kjmol-1. The reaction mechanism for 900 to 1100 °C temperature range corresponded to a nucleation and growing (P1.1) with an activation energy of 44.87 Kjmol-1. The activation energy was reduced in 35% for the samples that contained SrCO3 mechanically activated.La cinética de descomposición térmica del carbonato de Estroncio (SrCO3) en el sistema SrCO3-Al2O3-SrSO4 se estudió por medio de análisis térmico gravimétrico (ATG), utilizando el método isotérmico. Se prepararon mezclas de polvos 3:3:1 molar de SrCO3, Al2O3 y SrSO4 grado reactivo, las cuales fueron homogenizadas y tratadas a temperaturas entre 750 hasta 1100°C, por periodo de 4 horas. Adicionalmente se estudio el efecto del tiempo de activación mecánica del SrCO3 sobre la cinética de descomposición. Se obtuvieron curvas representativas de la pérdida de peso de las muestras al incrementar la temperatura, a partir de ellas se realizó el estudio cinético. Para el rango de temperatura de 750 a 900°C, el mecanismo de reacción que rige el proceso de descomposición corresponde a una contracción geométrica mediante la frontera de grano (R1.1) con una energía de activación (Ea) de 106.21KJmol-1. En el rango de temperatura de 950 a 1100°C, el mecanismo de reacción que rige la descomposición corresponde a un proceso de nucleación y crecimiento (P1.1), con un valor de Ea de 44.87KJmol-1. La energía de activación disminuye conforme se incrementa el tiempo de activado mecánico hasta un 35% para el caso de siete horas.

The mixed zinc-ferrite spinel magnetic nanoparticles (MNPs) with the general formula ZnxFe3−xO4 are among the most extensively studied families of Fe oxides due to their interesting and diverse chemical, electronic, and magnetic properties. These systems offer the possibility of surface functionalization and possess high biocompatibility, making them highly attractive for applications in biomedicine, such as magnetic fluid hyperthermia (MFH). The efficiency of the MFH process relies on the magnetic, structural and morphological properties of the MNPs. The substitution with the Zn ion and the cationic distribution, as well as the synthesis process employed, have a direct impact on the final properties of these oxides. Therefore, it is essential to have tools that enable a comprehensive characterization of the system to assess its performance in MFH. In this study, we have synthesized four ZnxFe3−xO4 MNP systems using three different methods: two by thermal decomposition at high temperatures, one by co-precipitation, and another by co-precipitation followed by ball milling. We analyze the effect of these various synthesis processes on the magnetic and crystallographic properties, aiming to correlate them with the response of each system in MFH. Neutron diffraction data are employed to determine the cation site occupation and to investigate the correlation with the synthesis method. MFH measurements were conducted in media of diverse viscosities, revealing different values of specific loss power, thus demonstrating a clear dependence on the synthesis process and Zn content. [ABSTRACT FROM AUTHOR]

Nuclides that are considered to be isotopes of element Z = 115 were produced in the reaction 48Ca + 243Am at the GSI Helmholtzzentrum für Schwerionenforschung Darmstadt. The detector setup TASISpec was used. It was mounted behind the gas-filled separator TASCA. Thirty correlated α-decay chains were found, and the energies of the particles were determined with high precision. Two important spectroscopic aspects of the offline data analysis are discussed in detail: the handling of digitized preamplified signals from the silicon strip detectors, and the energy reconstruction of particles escaping to upstream detectors relying on pixel-by-pixel dead-layer thicknesses.

Short-lived α-decaying nuclei "northeast" of Pb208 in the chart of nuclides were studied using the reaction Ca48+Am243 with the decay station TASISpec at TASCA, GSI Darmstadt. Decay energies and times from pile-up events were extracted with a tailor-made pulse-shape analysis routine and specific α-decay chains were identified in a correlation analysis. Decay chains starting with the even-even Ra220 and its odd-A neighbors, Fr219, and Ra221,219, with a focus on the Ra219→Rn215 decay, were studied by means of α-γ spectroscopy. A revised α-decay scheme of Ra219 is proposed, including a new decay branch from a previously not considered isomeric state at 17 keV excitation energy. Conclusions on nuclear structure are drawn from the experimental data, aided by Geant4 simulations and a discussion on theoretical calculations.

Short-lived α-decaying nuclei "northeast" of Pb208 in the chart of nuclides were studied using the reaction Ca48+Am243 with the decay station TASISpec at TASCA, GSI Darmstadt. Decay energies and times from pile-up events were extracted with a tailor-made pulse-shape analysis routine and specific α-decay chains were identified in a correlation analysis. Decay chains starting with the even-even Ra220 and its odd-A neighbors, Fr219, and Ra221,219, with a focus on the Ra219→Rn215 decay, were studied by means of α-γ spectroscopy. A revised α-decay scheme of Ra219 is proposed, including a new decay branch from a previously not considered isomeric state at 17 keV excitation energy. Conclusions on nuclear structure are drawn from the experimental data, aided by Geant4 simulations and a discussion on theoretical calculations.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non‐contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune‐mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti‐TNF therapy. These recommendations have extended to IL‐12/23, IL‐17, IL‐23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real‐world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL‐17 and IL‐23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN‐FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non‐biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management. [ABSTRACT FROM AUTHOR]

Context: For an ensiling to succeed, the knowledge about the factors that might influence the fermentation dynamics and nutrient loss is mandatory. One of the strategies is the use of additives such as tannins, as they can decrease proteolysis and increase the total organic acids. Aims: The aim was to investigate the effects of tannins on fermentation patterns and nutritional value of sorghum silage. Methods: Silages containing 0.0, 7.5, 15.0, 22.5, and 30.0 g/kg of tannin on fresh matter were studied. To produce the silage, the tannin was added to the forage and manually homogenised before ensiling. The study was conducted in three experiments. In the first experiment, five replications of each level of inclusion were produced and assigned in a completely randomised design. The chemical composition and fermentation patterns of all experimental units were evaluated. The second experiment consisted of analysing the aerobic deterioration by using a PET bottles system. This experiment was conducted in a completely randomised split plot, with five replications and five treatments with the inclusion of different levels of tannin (main plots) and the hours of exposure of silage to air (subplot). In the third experiment, five levels of tannin (main plots) and incubation times (subplots) were evaluated as for in situ digestibility (ruminal degradability) in a randomised blocks design with three replications (animals). Key results: The inclusion of tannins in sorghum silage caused quadratic effects on pH, acetic acid, lactic acid, total organic acids, ammonia nitrogen, dry matter content, crude protein content and in situ digestibility, when the level varied from 10.5 to 22.7 g tannin/kg fresh matter. There was a decreasing linear effect for aerobic deterioration as increasing levels of tannin in sorghum silage. Conclusions: The inclusion of tannin as an additive in sorghum silage is recommended for the production of good quality silage. The use of condensed tannins optimise fermentation patterns (especially increasing lactic acid and decreasing ammoniacal nitrogen), chemical composition, providing less aerobic deterioration and improve digestibility. Implications: This study revealed that condensed tannins can improve fermentation patterns and the nutritive value of sorghum silage. Tannins are secondary compounds that act to protect proteins from microbial degradation. Affinity between tannins and proteins is due to the presence of multiple phenolic hydroxyl groups in tannins, which promotes an easier connection with proteins. Tannins can decrease proteolysis in silage, inhibiting microbial action, through the protein-bound linkage in the ensiled mass. Thus, it is recommended to include of tannin as an additive in sorghum silage to improve fermentation patterns, diminish aerobic deterioration, as well as improve digestibility. [ABSTRACT FROM AUTHOR]

Products of the fusion-evaporation reaction 48Ca + 243Am were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany. Amongst the detected thirty correlated α-decay chains associated with the production of element Z=115, two recoil-α-fission and five recoil-α-α-fission events were observed. The latter five chains are similar to four such events reported from experiments performed at the Dubna gas-filled separator, and three such events reported from an experiment at the Berkeley gas-filled separator. The four chains observed at the Dubna gas-filled separator were assigned to start from the 2n-evaporation channel 289115 due to the fact that these recoil-α-α-fission events were observed only at low excitation energies. Contrary to this interpretation, we suggest that some of these recoil-α-α-fission decay chains, as well as some of the recoil-α-α-fission and recoil-α-fission decay chains reported from Berkeley and in this article, start from the 3n-evaporation channel 288115.

Produced in the reaction 48Ca+243Am, thirty correlated α-decay chains were observed in an experiment conducted at the GSI Helmholzzentrum für Schwerionenforschung, Darmstadt, Germany. The decay chains are basically consistent with previous findings and are considered to originate from isotopes of element 115 with mass numbers 287, 288, and 289. A set-up aiming specifically for high-resolution charged particle and photon coincidence spectroscopy was placed behind the gas-filled separator TASCA. For the first time, γ rays as well as X-ray candidates were observed in prompt coincidence with the α-decay chains of element 115.